The Brainstem Area Postrema may Not be Involved in Lithium-induced Activation of the Hypothalamic-pituitary-adrenal Axis

The brainstem area postrema (AP) has been suggested to be one potential site of lithium's action. In order to determine whether the AP, as a central action site of lithium, is involved in the hypothalamic-pituitary-adrenal (HPA) activation by lithium, we examined lithium-induced expression of inducible cAMP early repressor (ICER) gene in the adrenal gland of rat with lesion of AP. The adrenocortical ICER expression has been suggested to be a marker for the HPA axis activation. Sprague-Dawley rats with lesion or sham lesion of AP received intraperitoneal injection of 0.15 M LiCl at a dose of 12 ml/kg. One hour after the injection, rats were transcardially perfused with fixative and the adrenal glands were processed for ICER mRNA in situ hybridization. ICER mRNA levels in the adrenal cortex of sham lesion rats were significantly increased by lithium, compared to NaCl controls, and this increase was not affected by AP lesion. Our results suggest that the area postrema may not be involved in lithium's action to activate the HPA axis.